title: Gastric precancerous lesions are associated with gene variants in Helicobacter pylori-susceptible ethnic Malays.
abstract: OBJECTIVE
  To identify genes associated with gastric precancerous lesions in Helicobacter pylori (H. pylori)-susceptible ethnic Malays.
  
  
  METHODS
  Twenty-three Malay subjects with H. pylori infection and gastric precancerous lesions identified during endoscopy were included as "cases". Thirty-seven Malay subjects who were H. pylori negative and had no precancerous lesions were included as "controls". Venous blood was collected for genotyping with Affymetrix 50K Xba1 kit. Genotypes with call rates < 90% for autosomal single nucleotide polymorphisms (SNPs) were excluded. For each precancerous lesion, associated SNPs were identified from Manhattan plots, and only SNPs with a χ² P value < 0.05 and Hardy Weinberg Equilibrium P value > 0.5 was considered as significant markers.
  
  
  RESULTS
  Of the 23 H. pylori-positive subjects recruited, one sample was excluded from further analysis due to a low genotyping call rate. Of the 22 H. pylori-positive samples, atrophic gastritis only was present in 50.0%, complete intestinal metaplasia was present in 18.25%, both incomplete intestinal metaplasia and dysplasia was present in 22.7%, and dysplasia only was present in 9.1%. SNPs rs9315542 (UFM1 gene), rs6878265 (THBS4 gene), rs1042194 (CYP2C19 gene) and rs10505799 (MGST1 gene) were significantly associated with atrophic gastritis, complete intestinal metaplasia, incomplete metaplasia with foci of dysplasia and dysplasia, respectively. Allele frequencies in "cases" vs "controls" for rs9315542, rs6878265, rs1042194 and rs10505799 were 0.4 vs 0.06, 0.6 vs 0.01, 0.6 vs 0.01 and 0.5 vs 0.02, respectively.
  
  
  CONCLUSIONS
  Genetic variants possibly related to gastric precancerous lesions in ethnic Malays susceptible to H. pylori infection were identified for testing in subsequent trials.
authors.affiliation: School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Malaysia.
authors.forename: Sathiya
authors.initials: S
authors.lastname: Maran
authors.forename: Yeong Yeh
authors.initials: YY
authors.lastname: Lee
authors.forename: Shuhua
authors.initials: S
authors.lastname: Xu
authors.forename: Nur-Shafawati
authors.initials: NS
authors.lastname: Rajab
authors.forename: Norhazrini
authors.initials: N
authors.lastname: Hasan
authors.forename: Syed Hassan
authors.initials: SH
authors.lastname: Syed Abdul Aziz
authors.forename: Noorizan Abdul
authors.initials: NA
authors.lastname: Majid
authors.forename: Bin Alwi
authors.initials: BA
authors.lastname: Zilfalil
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005757:Gastritis, Atrophic / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000382:microbiology; D005773:Gastroscopy; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications* / Q000175:diagnosis / Q000208:ethnology / Q000382:microbiology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D008296:Malaysia / Q000453:epidemiology; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011230:Precancerous Conditions / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000382:microbiology; D011237:Predictive Value of Tests; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000382:microbiology
keywords: Gastric precancerous lesions; Gene polymorphisms; Genome-wide association; Helicobacter pylori; Malays